Perinatal nutritional iron deficiency impairs noradrenergic-mediated synaptic efficacy in the CA1 area of rat hippocampus

Abstract

Many studies have shown that perinatal nutritional iron deficiency (ID) produces learning impairments in children. Research has also shown that catecholamines like epinephrine and norepinephrine play a pivotal role in the consolidation of memories. In this study, we sought to determine if perinatal ID impairs the following: 1) noradrenergic synaptic function in the hippocampus; and 2) several forms of hippocampus-dependent fear learning. Electrophysiological brain slice methods were used to examine noradrenergic-mediated synaptic efficacy in the CA1-hippocampus of rats that were subjected to perinatal ID or control (CN) diets. Rats were fed ID (3 mg Fe/kg) or CN (45 mg Fe/kg) diets on gestational d 14. These diets were maintained until postnatal d (P) 12 after which all rats were switched to the CN diet. Hippocampal slices were prepared between P26 and P30. The noradrenergic agonist isoproterenol (ISO) (1, 2, or 4 micromol) was used to induce modulatory increases in synaptic efficacy in the hippocampal slices. CN slices showed a long-lasting increase in synaptic efficacy as the result of ISO perfusion in the slice bath, whereas ID slices did not show increases in synaptic efficacy as the result of ISO perfusion. ID and CN groups did not differ when ISO was perfused through slices from adult rats (P61). Both young and adult ID rats showed reduced levels of hippocampus-dependent fear learning compared with the young and adult CN rats. Together, these findings suggest that ID may impair early forms of noradrenergic-mediated synaptic plasticity, which may in turn play a role in adult learning deficits.

FIGURE 1

Population spike amplitude recorded from the CA1 area of hippocampal slices from young p26–30 rat pups before, during, and after perfusion with 4 (A), 2 (B), or 1 (C) umol/L ISO. The 10-min ISO perfusion period is indicated by the open bar starting at the 10-min mark. Insets show exemplar population spikes immediately before and 20-min after the start of ISO perfusion (calibration bars: 5 ms, 1 mV). Each slice was subjected to only 1 ISO concentration. Values are means ± SEM with the number of slices is shown in each panel. *Different from ID at these times, P < 0.05.

FIGURE 2

Population spike amplitude recorded from the CA1 area of adult P61–65 slices before, during, and after perfusion of 2 concentrations of ISO (A and B). The 10-min ISO perfusion period is indicated by the open bar starting at the 10-min mark. Insets show exemplar population spikes immediately before and 20-min after the start of ISO perfusion. Values are means ± SEM with the number of slices shown in each panel. Each slice was subjected to only a single ISO concentration.

FIGURE 3

Freezing-fear responses for trace and contextual fear memory tests for the young (A and B) and adult groups (C and D). The presentation of the tone-CS is shown by the open bar in A and C. Values are means ± SEM with the number of slices shown in each panel.